Inflammatory Bowel Disease, Ulcerative Colitis (UC)
Conditions
Keywords
Fecal microbiota transplantation, Ulcerative colitis, Inflammatory bowel disease, Dai donors, Han donors, Gut microbiota, Clinical efficacy
Brief summary
This study is a randomized clinical trial evaluating fecal microbiota transplantation (FMT) for ulcerative colitis (UC) using healthy donors from two ethnic groups in Yunnan, China. UC is a chronic inflammatory bowel disease causing colon inflammation and ulcers. FMT transfers gut bacteria from a healthy donor to a patient to restore healthy intestinal microbiota. Previous research suggested that FMT using donors from the Dai ethnic group (a minority nationality in Yunnan with special dietary habits) may achieve better results than Han Chinese donors for UC. This study aims to confirm this finding and understand why. The investigators will recruit 200 UC patients (ages 18-60) and randomly assign them to two groups (100 each). One group will receive FMT from healthy Han donors; the other from healthy Dai donors. Patients will receive three FMT infusions via endoscopic intestinal tubing. Treatment effects will be assessed at 12 weeks using clinical scores (Mayo score), endoscopic scores (MES), inflammatory markers (fecal calprotectin, CRP, ESR), and intestinal barrier function tests. Stool samples will also be analyzed using metabolomics and metagenomics to identify key gut bacteria and metabolites linked to better outcomes, and laboratory experiments will be performed to verify how they reduce intestinal inflammation. The goal is to identify optimal donor characteristics for FMT in UC and uncover mechanisms that may lead to more personalized microbiota therapies.
Detailed description
This randomized, parallel-group clinical study investigates the efficacy and mechanisms of fecal microbiota transplantation (FMT) using healthy donors from the Dai nationality versus Han nationality for treating ulcerative colitis (UC). Background: UC is a chronic relapsing inflammatory bowel disease characterized by colonic mucosal inflammation. FMT has emerged as a promising therapeutic strategy by reconstructing intestinal microbiota. Preliminary findings indicate that FMT using donors from the Dai ethnic group in Yunnan Province (who have unique dietary and lifestyle habits) may achieve superior clinical remission compared to Han donors. This study aims to validate this observation and identify the core metabolites and key gut microbiota responsible for the enhanced efficacy. Study Design: A total of 200 UC patients (aged 18-60 years, Mayo score 3-10, left-sided colitis) will be enrolled and randomly allocated into two groups (n=100 each): (1) FMT with healthy Han donors; (2) FMT with healthy Dai donors. Donors will be healthy individuals aged 18-23 years screened according to AGA guidelines. Intervention: Patients will receive FMT via transendoscopic enteral tubing (TET) at 60 mL per infusion, once every 3 days for a total of 3 times. Outcome Measures: Primary efficacy is clinical remission at week 12 (Mayo total score ≤2, no individual subscore \>1, endoscopic subscore decreased by ≥1 from baseline). Secondary endpoints include Mayo score, MES, histopathology (HE staining), fecal calprotectin, CRP, ESR, and intestinal mucosal barrier function. Mechanistic Investigations: Donor and recipient stool samples will be collected before FMT and at weeks 1 and 12 post-FMT. Metabolomics (LC-MS/MS, GC-MS) and metagenomic sequencing will identify differential metabolites and key bacterial taxa. Co-occurrence and metabolic complementarity networks will identify keystone species. Correlation analysis will reveal functional microbial groups. In vitro and in vivo experiments will validate the anti-inflammatory effects of identified key bacteria and metabolites. Significance: This study will elucidate why Dai donors may confer superior FMT outcomes and identify transplantable microbial signatures and bioactive metabolites for UC therapy.
Interventions
BIOLOGICALFecal Microbiota Transplantation (FMT)
Donor stool (60 g) is processed using the CleanFMT method with GenFMTer system, including filtration, centrifugation, washing, and resuspension in sterile normal saline (1.5× volume). The final product is 200 mL fecal suspension, administered via TET at 60 mL per session, once every 3 days, for 3 sessions total.
Sponsors
First Affiliated Hospital of Kunming Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label study. Both participants and care providers are aware of the donor group assignment.
Intervention model description
Patients with ulcerative colitis are randomly assigned to receive fecal microbiota transplantation (FMT) from either Dai donors or Han donors in a parallel group design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-60 years * Diagnosed with ulcerative colitis (left-sided colitis) according to ECCO guidelines and Chinese Guidelines for the Diagnosis and Treatment of Ulcerative Colitis (2023 Xi'an) * Baseline Mayo score 3-10 * Treated only with mesalazine before and during the study to exclude drug interference
Exclusion criteria
* Pregnancy or planned pregnancy in the near future * Patients in clinical remission (Mayo score ≤2 with no individual subscore \>1) * Development of diseases different from or confounding the initial diagnosis during the study * History of toxic megacolon, perianal disease, or intestinal surgery * Concurrent severe cardiac, pulmonary, or renal disease, or malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of clinical and endoscopic remission at 12 weeks | 12 weeks after the first FMT session | Proportion of ulcerative colitis patients achieving both clinical and endoscopic remission at 12 weeks after fecal microbiota transplantation (FMT) without corticosteroid use. Clinical remission is defined as a total Mayo score ≤2 with no individual subscore \>1. Endoscopic improvement is defined as a decrease in the Mayo Endoscopic Subscore (MES) of at least 1 point from baseline. Patients must achieve both criteria simultaneously. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mayo Score | Baseline (1 day pre-FMT), 1 week, and 12 weeks post-FMT | Change from baseline in total Mayo score (range 0-12, higher scores indicate more severe disease activity). |
| Mayo Endoscopic Subscore (MES) | Baseline and 12 weeks post-FMT | Change from baseline in MES (range 0-3, where 0=normal/remission, 1=mild, 2=moderate, 3=severe). |
| Histopathological Assessment by HE Staining | Baseline and 12 weeks post-FMT | Histological changes in colonic mucosal biopsies assessed by HE staining. |
| Fecal Calprotectin | Baseline, 1 week, and 12 weeks post-FMT | Change from baseline in fecal calprotectin levels as a marker of intestinal inflammation. |
| C-Reactive Protein (CRP) | Baseline, 1 week, and 12 weeks post-FMT | Change from baseline in serum CRP levels. |
| Erythrocyte Sedimentation Rate (ESR) | Baseline, 1 week, and 12 weeks post-FMT | Change from baseline in ESR. |
| Intestinal Mucosal Barrier Function | Baseline and 12 weeks post-FMT | Assessment of intestinal mucosal barrier function in UC patients after FMT. |
Countries
China
Contacts
CONTACTZihong Chen
PRINCIPAL_INVESTIGATORYinglei Miao, MD
Kunming Medical University First Affiliated Hospital
Outcome results
None listed